1. Field of the Invention
The invention relates to synthetic methods for producing macrocyclic compounds, and more particularly, to synthetic methods for producing tetraamido macrocyclic ligands and metal chelate complexes as pre catalysts for oxidation reactions.
2. Description of the Invention Background
Complexes of high oxidation state transition metals are known to function as oxidants in numerous biological reactions under the influence of a protein matrix and in recent years a widespread interest in understanding the mechanism of action and the reactivity of certain monooxygenase catalysts has developed. However, in the absence of a protein matrix to direct the oxidizing power towards a specific substrate, high oxidation state transition metal complexes tend to exhibit low oxidative selectivity and will instead oxidize any available substrate. Since the ligand complement is available in high local concentration as a possible substrate, oxidative degradation of the ligand complement has been a formidable impediment to obtaining long lived oxidation catalysts in the absence of a stabilizing matrix.
Collins, T. J., "Designing Ligands for Oxidizing Complexes," Accounts of Chemical Research, 279, Vol. 27, No. 9 (1994), describes a design oriented approach for obtaining ligands that are resistant to oxidative degradation when coordinated to highly oxidizing metal centers. Several diamido-N-diphenoxido and diamido-N-alkoxido acyclic chelate compounds and macrocyclic tetraamido-N chelate compounds are described in the Collins Accounts of Chemical Research article.
An azide based synthetic route to macrocyclic tetraamido ligands is described in Uffelman, E. S., Ph.D. Thesis, California Institute of Technology, (1992). Synthesis of the tetraamido ligands via the azide based route developed by Uffelman proceeds generally as follows: ##STR1##
Synthesis of an aryl bridged tetraamido ligand via the azide based route proceeds as follows: ##STR2## 5,6: (4,5-Di-X-Benzo) -3,8,11,13-tetraoxo-2,2,9,9-tetramethyl-12,12-diethyl-1,4,7,10-tetraazacyc lotridecane (or Tetramethyl diethyl di-X-benzene (TMDE-DXB, where X=Cl, H, Me, OMe))
The yield of the azide based method is about 25% for the final ring closing step but only about 5-10% for the combined sequence of steps starting from the diamine. This method generates new C--N bonds via formation of azide intermediates. The generation of the C--N bonds, however, is not very effective, at least as to yield. With each step of the process, the yield is reduced further so that the overall yield of the desired tetraamido ligand is comparatively low. Furthermore, the azide based method produces high energy intermediates.
There is a need for an alternative method of producing tetraamido ligands. There is also a need to improve the yield of such ligands. Finally, there is a need for a method of producing tetraamido ligands that are resistant to oxidative degradation and in which the various substituent groups can be controlled to tailor the ligands and the metallo complexes they form for specific end uses.